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Review
Wilson’s disease: update on pathogenesis, biomarkers and treatments
  1. Samuel Shribman1,
  2. Aurelia Poujois2,
  3. Oliver Bandmann3,
  4. Anna Czlonkowska4,
  5. Thomas T Warner1
  1. 1 Reta Lila Weston Institute, UCL Queen Square Institute of Neurology, London, UK
  2. 2 Department of Neurology, National Reference Centre for Wilson's Disease, Rothschild Foundation Hospital, Paris, France
  3. 3 Department of Neuroscience, Sheffield Institute for Translational Neuroscience, Sheffield, UK
  4. 4 Second Department of Neurology, Institute of Psychiatry and Neurology, Warsaw, Poland
  1. Correspondence to Dr Samuel Shribman, Reta Lila Weston Institute, UCL Queen Square Institute of Neurology, London, UK; s.shribman{at}ucl.ac.uk

Abstract

Wilson’s disease is an autosomal–recessive disorder of copper metabolism caused by mutations in ATP7B and associated with neurological, psychiatric, ophthalmological and hepatic manifestations. Decoppering treatments are used to prevent disease progression and reduce symptoms, but neurological outcomes remain mixed. In this article, we review the current understanding of pathogenesis, biomarkers and treatments for Wilson’s disease from the neurological perspective, with a focus on recent advances. The genetic and molecular mechanisms associated with ATP7B dysfunction have been well characterised, but despite extensive efforts to identify genotype–phenotype correlations, the reason why only some patients develop neurological or psychiatric features remains unclear. We discuss pathological processes through which copper accumulation leads to neurodegeneration, such as mitochondrial dysfunction, the role of brain iron metabolism and the broader concept of selective neuronal vulnerability in Wilson’s disease. Delayed diagnoses continue to be a major problem for patients with neurological presentations. We highlight limitations in our current approach to making a diagnosis and novel diagnostic biomarkers, including the potential for newborn screening programmes. We describe recent progress in developing imaging and wet (fluid) biomarkers for neurological involvement, including findings from quantitative MRI and other neuroimaging studies, and the development of a semiquantitative scoring system for assessing radiological severity. Finally, we cover the use of established and novel chelating agents, paradoxical neurological worsening, and progress developing targeted molecular and gene therapy for Wilson’s disease, before discussing future directions for translational research.

  • Wilson's disease

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Footnotes

  • Contributors SS wrote the first draft of the manuscript. AP, OB, AC and TTW revised the manuscript.

  • Funding SS is funded by the Guarantors of Brain, Association of British Neurologists and Reta Lila Weston Institute (no award/grant numbers).

  • Competing interests None declared.

  • Provenance and peer review Commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

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